Methods for controlling cell-type by dedifferentiation, directed differentiation, and transdifferentiation or direct reprogramming have enabled the generation, in the laboratory, of tissue-specific, patient-specific cells from small, non-invasive skin samples. However, critical roadblocks have so far prevented these methods from being used to generate large screening libraries. Existing cell-reprogramming technologies are slow and inefficient, using either integrating viruses, which carry risks of insertional mutagenesis and spontaneous oncogene reactivation, or non-viral vectors with even lower efficiencies. Factor Bioscience has developed the first rapid, reliable, DNA-free technology for reprogramming adult cells. In this project, we will apply this technology to generate a library of cells capable of generating neurons from patients with and without Alzheimer's disease. Furthermore, we will use our patented gene-editing technology to confer Alzheimer's- associated mutations to healthy patient samples, creating the first isogenic library for screening drugs to treat or preven Alzheimer's disease. PUBLIC HEALTH RELEVANCE: This project will develop the first library of gene-edited neurons developed from patient cells in order to model Alzheimer's-disease-associated mutations in an isogenic background. The results of this project will enable more accurate drug screening for the treatment and prevention of Alzheimer's disease.